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The Role of Gut Microbiota in Hypertension

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ClinicalTrials.gov Identifier: NCT02188381
Recruitment Status : Recruiting
First Posted : July 11, 2014
Last Update Posted : February 5, 2021
Sponsor:
Collaborator:
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
University of Florida

Tracking Information
First Submitted Date July 9, 2014
First Posted Date July 11, 2014
Last Update Posted Date February 5, 2021
Actual Study Start Date July 2014
Estimated Primary Completion Date October 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: July 9, 2014)
  • Characterize gut microbiota composition at phylum level [ Time Frame: 24 hours ]
    Stool samples to analyze the composition of the microbiota, extracted bacterial genomic DNA will be used as a template for PCR reactions targeting the V4-V5 variable regions of the 16S rRNA gene. Amplicons generated from the PCR will be run on the Illumina MiSeq sequencing platform available in our laboratory to profile microbial communities at phylum level.
  • Characterize gut microbiota composition at genus level [ Time Frame: 24 hours ]
    Stool samples to analyze the composition of the microbiota, extracted bacterial genomic DNA will be used as a template for PCR reactions targeting the V4-V5 variable regions of the 16S rRNA gene. Amplicons generated from the PCR will be run on the Illumina MiSeq sequencing platform available in our laboratory to profile microbial communities at genus level.
Original Primary Outcome Measures Same as current
Change History
Current Secondary Outcome Measures
 (submitted: August 23, 2018)
  • Reduction in BP is associated with changes in gut microbiota composition in RH subjects. [ Time Frame: Baseline, 3 months ]
    Stool samples from patients enrolled in NCT 02133871 that received minocycline medication for resistant hypertension. Will be used to analyze the composition of the microbiota and data (taxonomic assignment) will be analyzed using QIIMEv1.3 pipeline to enumerate microbial population between samples derived from the cohorts.
  • IS hypertension associated with increased sympathetic activity and decreased parasympathetic activity and whether minocycline or other tetracyclines are effective to improve this balance [ Time Frame: Baseline and 3 months ]
    Stool samples from patients enrolled in NCT 02133871 that received minocycline
  • To determine if characterization of gut microbiota in at risk patients predicts long term care utilization and/or cardiovascular outcomes [ Time Frame: Up to 5 years ]
    Stool samples
Original Secondary Outcome Measures
 (submitted: July 9, 2014)
Reduction in BP is associated with changes in gut microbiota composition in RH subjects. [ Time Frame: Baseline, 3 months ]
Stool samples from patients enrolled in NCT 02133871 that received minocycline medication for resistant hypertension. Will be used to analyze the composition of the microbiota and data (taxonomic assignment) will be analyzed using QIIMEv1.3 pipeline to enumerate microbial population between samples derived from the cohorts.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title The Role of Gut Microbiota in Hypertension
Official Title The Role of Gut Microbiota in Hypertension: Brain-Gut Microbiome-Immune Axis in Hypertension
Brief Summary Hypertension is the single most prevalent risk factor for heart diseases, heart failure, kidney failure and stroke. About 1 in 3 adults in the United States have hypertension. Approximately 28-30% of hypertensive patients suffer from resistant hypertension (RH). Inflammation has been implicated in the pathogenesis of the hypertension. Additional data suggests the involvement of gut microbiota in host normal cardiovascular functions and pathophysiology. Accumulating evidence demonstrates that antibiotic treatment benefits patients with acute coronary syndromes and reduces the incidence of ischemic cardiovascular events. Even though these studies did not address effects of antibiotic treatment on the gut microbiota, it is possible that gut microbiota could affect neurologic inflammation. Finally, intestinal microbiota has recently been proposed to modulate blood pressure (BP) through production of short-chain fatty acids. In order to investigate this, the investigators hypothesize that gut microbiota is involved in the neuroinflammation-mediated initiation and establishment of RH, and targeting gut microbiota by minocycline would produce beneficial outcomes in RH.
Detailed Description This is a prospective cohort design. This study will enroll 388 subjects: 81 patients without HTN as a reference group, 81 patients with controlled HTN, 55 patients with uncontrolled HTN, 55 with remodeled RH, and 81 patients with RH to characterize gut microbiota composition. Subjects will provide stool samples for analysis. Subjects will also provide a blood sample for inflammatory marker and stem cell analysis.
Study Type Observational
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples With DNA
Description:
Stool Samples
Sampling Method Non-Probability Sample
Study Population This study will initially enroll 10 patients without hypertension as normal controls, and 10 patients with controlled hypertension and 10 patients with resistant hypertension to characterize gut microbiota. In addition, all patients enrolled in IRB# 102-2013 will be approached for possible participation.
Condition Hypertension
Intervention Other: Stool Sample and Blood Sample
All subjects will provide a stool sample and a blood sample at baseline. Subjects in NCT02133872 will provide a second stool sample and blood sample at their 3 month visit.
Study Groups/Cohorts
  • Normal controls without hypertension
    Control subjects will have a systolic BP <140mmHg with no cardiovascular disease. These subjects will provide a one time stool sample and a blood sample.
    Intervention: Other: Stool Sample and Blood Sample
  • Controlled hypertension
    Subjects with controlled hypertension will provide a one time stool sample and a blood sample.
    Intervention: Other: Stool Sample and Blood Sample
  • Resistant hypertension
    Resistant hypertension subjects will have systolic blood pressure (BP) ≥140 mmHg despite ≥3 anti-hypertensive medications of different classes. These subjects will provide a one time stool sample and a blood sample.
    Intervention: Other: Stool Sample and Blood Sample
  • Prior enrolled in NCT 02133872
    These subject will be asked to provide two stool samples and two blood samples. One at baseline and one after 3 months of therapy.
    Intervention: Other: Stool Sample and Blood Sample
  • Remodeled Resistent Hypertension
    Subjects with controlled hypertension will provide a one time stool sample and a blood sample.
    Intervention: Other: Stool Sample and Blood Sample
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Recruiting
Estimated Enrollment
 (submitted: February 13, 2019)
426
Original Estimated Enrollment
 (submitted: July 9, 2014)
78
Estimated Study Completion Date October 2023
Estimated Primary Completion Date October 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria

Inclusion Criteria:

  • age >18 and <80
  • is competent and willing to provide consent

Inclusion criteria for each subject group:

  • Control subjects will have a systolic BP <140mmHg with no cardiovascular disease
  • Patients with controlled hypertension
  • Patients with uncontrolled hypertension
  • Resistant hypertension subjects will have systolic blood pressure (BP) ≥140 mmHg despite ≥3 anti-hypertensive medications of different classes one of which should be a diuretic
  • Patients who are no longer RH subjects and have normal blood pressure
  • Subjects participating in NCT 02133872 will be eligible to participate

Exclusion Criteria:

  • currently pregnant or have been pregnant in the last 6 months;
  • antibiotic treatment within 2 months of study enrollment;
  • currently taking a medication (e.g., antibiotic, anti-inflammatory agents, glucocorticoids or other immune modulating medications);
  • unwilling to discontinue vitamin or supplements, including probiotics, potentially affecting gut microbiota (vitamins/supplements and medications that possibly affect the gut microbiota should be discontinued for at least 2wks prior to stool collection);
  • history of intestinal surgery, inflammatory bowel disease, celiac disease, lactose intolerance, chronic pancreatitis or other malabsorption disorder.
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers Yes
Contacts
Contact: Eileen M Handberg, PhD 352-273-8944 handbem@ufl.edu
Listed Location Countries United States
Removed Location Countries  
 
Administrative Information
NCT Number NCT02188381
Other Study ID Numbers IRB201400233-N
1R01HL132448-01 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement Not Provided
Responsible Party University of Florida
Study Sponsor University of Florida
Collaborators National Heart, Lung, and Blood Institute (NHLBI)
Investigators
Principal Investigator: Carl Pepline, MD University of Florida
PRS Account University of Florida
Verification Date February 2021